14B21: Exam Report
Compare and contrast the pharmacology of haloperidol and diazepam.
50% of candidates passed this question.
These are both commonly used agents and a tabulated format worked well. Subheadings covering the “general” pharmacology approach ensured core areas were addressed. Vague terms such as “good” or “moderate” did not allow a detailed comparison between the agents. Repetition of facts between sections such as uses, pharmacodynamics, effects and adverse
effects did not gain further marks.
K2iv / 14B21: Compare and contrast the pharmacology of Haloperidol and Diazepam
Drug
Haloperidol
Diazepam
Use
Haloperidol
- Delirium & agitation in ICU
- Schizophrenia
- N&V
Diazepam
- Anxiety
- AWS
- Epilepsy
- Sedation
- Premed
Both used for agitation in ICU setting
Diazepam has a more robust profile especially for patients with Hx ETOH XS
Route
Haloperidol
PO/IV/IM
Diazepam
PO, IV, PR, IM (erratic absorption, muscle necrosis)
Similar routes of admin
MoA
Haloperidol
Central dopaminergic blockade
Post synaptic GABA antagonism
Diazepam
Binds BZD receptor – closely linked with GABA receptor
Facilitates GABA-ergic transmission
↑frequency of Cl– channel opening
Different MoAs
PD
Haloperidol
CNS
- ↓motor activity
- Anxiolysis
- ↑seizure threshold
- Indifference to external environment
CVS – ↓BP (some α1 antagonism)
GI – antiemesis (powerful) by ↑vomiting threshold @ CTZ
Diazepam
CNS – sedation, amnesia, anticonvulsant, anxiolysis
CVS – transient ↓BP + CO, ↓myocardial O2 consumption, ↓sensitivity of BaroR
Resp – Resp D 2° ↓VT, ↓response to ↑PaCO2, occasional apnoea
MSK – ↓skeletal m. tone
Both cause similar neuro effects
BP effects of Haloperidol less marked
Significant respiratory SE of Diazepam
BZD well known for reducing sk m tone if this is desired also
Haloperidol well established as an antiemetic
PK
Haloperidol
A
OBA 60%
D
90% PPB
VD 9 – 20L/kg
M
Liver glucuronidation then reduction
(some) active metabolites
E
Metabolites via urine
15% faeces
t ½ B 10 – 45hrs
Diazepam
A
85% OBA
D
99% PPB
VD 1.5L/kg → large because deposits itself in fat
∴ prolonged DoA in elderly & women (↑fat content)
M
Liver OXIDATION
2 active metabolites
E
Desmethyldiazepam is oxidised & metabolites excreted in urine
Diaz has rapid oral absorption and onset w prolonged activity
Both metabolised in the liver
Diazepam has a prolonged DoA owed to its active metabolites
Adverse Effects
Haloperidol
- Hypotension
- Abnormal LFTs
- GI & haematopoietic disturbances
EXTRAPYRAMIDAL → NMS
Diazepam
- Tolerance
- Dependence
- Ataxia
- Headache
- GI upset
- Rashes
IV = highly irritant to veins
Diazepam a drug of abuse
Risk of extrapyramidal se w haloperidol and requires monitoring of bloods